Patients with cancer represent a major challenge for venous thromboembolism (VTE) treatment because of their higher risk of major bleeding and other factors that change with the patient, cancer and treatment.
Low-molecular-weight heparin (LMWH) has long been the preferred treatment recommended by the practice guidelines. Recently, the National Comprehensive Cancer Network (NCCN) proposed direct oral anticoagulants (DOACs) as the treatment of choice for patients without gastric or gastroesophageal cancer .
In addition, the American Society of Clinical Oncology (ASCO) guidelines recommend DOACs and LMWH for long-term anticoagulation for cancer-associated thrombosis (CAT; over vitamin K antagonists), noting caution with DOACs for gastrointestinal and potentially genitourinary malignancies .
Caution on the use of DOACs in patients with gastrointestinal cancers is mandatory since a few studies reported a higher rate of major bleeding complications among these patients [3,4].
NCCN guidelines recommend DOACs as initial therapy for VTE in ambulatory patients with cancer with an intact upper gastrointestinal tract and hospitalized patients with cancer for whom surgical intervention is not planned .
On the contrary, LMWH should be preferred as the initial therapy for VTE in ambulatory patients with gastrointestinal or genitourinary malignancies with luminal lesions who cannot take oral medications or lack an intact upper gastrointestinal tract. However, LMWH should also be the treatment of choice for ambulatory or hospitalized patients whose anticancer therapy has significant drug interactions with DOACs or patients who have thrombocytopenia <50,000 cells/L, with a dose reduction recommended for platelets in the range of 25,000–50,000 cells/L. Finally, LMWH should be used in hospitalized patients for whom surgical intervention is planned .
Patients with CAT should undergo anticoagulation therapy for a minimum of 6 months and should continue it until the cancer is active or under treatment or in the presence of persistent risk factors for recurrent VTE .
Independently from the treatment used, patients’ adherence is a key factor for the therapy’s success. It may be argued that adherence and persistency could be higher in patients using DOACs because more comfortable and cheaper compared to the LMWH subcutaneous therapy.
Importantly, adherence is the ability of the patient to stick with the medication assigned, while persistency is the capability of continuing the medication for a long time.
A few studies evaluated and compared cancer patients’ persistence and adherence using DOACs or LMWH.
A comparison of LMWH to DOACs
A recent retrospective cohort study investigated the effect of anticoagulant class on medication adherence for CAT, using Optum’s de-identified Cliniformatics® Data Mart. Cliniformatics® Data Mart is a large commercial and Medicare Advantage claims database containing data on more than 61 million privately insured individuals .
A total of 4,570 patients with active cancer and an episode of CAT were involved in the study: 2,580 patients were treated with LMWH and 1,570 with DOACs.
Patients on DOACs and LMWH were compared using pharmacy claims data to assess patient persistence on their initial anticoagulant and the proportion of days covered (PDC) as a surrogate for anticoagulant adherence.
Medication adherence was defined as a PDC ≥80%. Two sensitivity analyses were conducted, one defining medication adherence as PDC ≥95% and one comparing mean PDC between the two groups to evaluate adherence as a continuous variable .
The analysis suggests that a high proportion of cancer patients are adherent to the anticoagulant class prescribed, with no differences between DOACs and LMWH. This indicates that although DOACs might be a more comfortable choice, adherence does not differ between the two classes of anticoagulants.
No significant difference in adherence was highlighted between LMWH and DOACs when adherence is defined as PDC ≥80% or compared by mean PDC. When adherence is defined as PDC ≥95%, it was greater for patients using LMWH than DOACs.
However, patients using DOACs seemed to have a higher persistence. More than half of the patients using LMWH transitioned to another anticoagulant class by 3 months of treatment, probably due to cost or the desire to avoid injections .
Patients were followed-up for a median of 72 days (interquartile range [IQR]: 30–170 days), and those using DOACs remained under the same regimen for a median of 116 days (IQR: 57–231 days) while those using LMWH persisted for a median of 34 days (IQR: 30–92 days). The median treatment persistence on DOACs was more than 80 days longer than LMWH.
Regarding costs, the average prescription copayment for 30 days of medication supplied was higher for patients treated with LMWH (mean $153.61, standard deviation $306.74) compared to those treated with DOAC (mean $ 40.67; standard deviation $33.11).
On average, patients using LMWH payed more than $100 more per month than DOACs for their therapy. Considering the high cost associated with cancer treatment, the added cost of LMWH may contribute to the lower patient persistence on LMWH than DOACs .
In all, the results of this study oppose the diffuse perception that patients might be less adherent to an LMWH regimen compared to DOACs but highlight a minor persistence to LMWH probably due to a mix of factors like costs and drug administration route.
Because of a lower persistence compared to DOACs, when assigning LMWH, clinicians should regularly re-assess the optimal anticoagulant for their patients over time.
- Streiff MB, Holmstrom B, Angelini D, et al. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines), Cancer-Associated Venous Thromboembolic Disease. Version 1.2020. April 16, 2020. www.nccn.org/professionals/physician_gls/pdf/vte.pdf.
- Key NS, Khorana AA, Kuderer NM, et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: ASCO clinical practice guideline update. J Clin Oncol. 2020;38:496-520.
- Young AM, Marshall A, Thirlwall J, et al. Comparison of an Oral Factor Xa Inhibitor With Low Molecular Weight Heparin in Patients With Cancer With Venous Thromboembolism: Results of a Randomized Trial (SELECT-D). J Clin Oncol. 2018;36(20):2017-2023.
- Kraaijpoel N, Di Nisio M, Mulder FI, et al. Clinical Impact of Bleeding in Cancer-Associated Venous Thromboembolism: Results from the Hokusai VTE Cancer Study. Thromb Haemost. 2018;118(8):1439-1449.
- O’Connell C, Escalante CP, Goldhaber SZ, McBane R, Connors JM, Raskob GE. Treatment of Cancer-Associated Venous Thromboembolism with Low-Molecular-Weight Heparin or Direct Oral Anticoagulants: Patient Selection, Controversies, and Caveats. Oncologist. 2021;26(1):e8-e16.
- Schaefer JK, Li M, Wu Z, et al. Anticoagulant medication adherence for cancer-associated thrombosis: A comparison of LMWH to DOACs. J Thromb Haemost. 2021;19(1):212-220.